Alpha cells secrete the peptide hormone glucagon in order to increase glucose levels in the blood stream.
They discovered that "insulin-induced hypoglycemia was preceded by a transient, rather mild hyperglycemia..."[4] Murlin is credited with the discovery of glucagon because in 1923 they suggested that the early hyperglycemic effect observed by Banting and Best was due to "a contaminant with glucogenic properties that they also proposed to call 'glucagon,' or the mobilizer of glucose".
Alpha cells store this glucagon in secretory vesicles that typically have an electron dense core and a grayish outer edge.
Alpha cells are stimulated to produce glucagon in response to hypoglycemia, epinephrine, amino acids, other hormones, and neurotransmitters.
[5] Glucagon functions to signal the liver to begin gluconeogenesis which increases glucose levels in the blood.
The most well studied is through the action of extra-pancreatic glucose sensors, including neurons found in the brain and spinal cord, which exert control over the alpha cells in the pancreas.
[5] The most well studied is through the action of extra-pancreatic glucose sensors, including neurons found in the brain, which exert control over the alpha cells in the pancreas.
[9] According to Travagli et al. "axons from these neurons exit the spinal cord through the ventral roots and supply either the paravertebral ganglia of the sympathetic chain via communicating rami of the thoracic and lumbar nerves, or the celiac and mesenteric ganglia via the splanchnic nerves.
It appears that stimulation of the splanchnic nerve lowers plasma insulin levels possibly through the action of α2 adrenoreceptors on beta cells.
[9] Both of these findings together suggest that sympathetic stimulation of the pancreas is meant to maintain blood glucose levels during heightened arousal.
[8] Electrical and pharmacological stimulation of the Vagus nerve increases secretion of glucagon and insulin in most mammalian species, including humans.
It has been proposed to act as a paracrine signal to inhibit glucagon secretion in alpha cells.
[10] Insulin has been shown to function as a paracrine signal to inhibit glucagon secretion by the alpha cells.
If the concentration of ATP drops in alpha cells, this causes potassium ion channels in the plasma membrane to close.
[15] It is thought that high glucagon levels and lack of insulin production are the main triggers for the metabolic issues associated with Type I diabetes, in particular maintaining normal blood glucose levels, formation of ketone bodies, and formation of urea.
[16] One finding of note is that the glucagon response to hypoglycemia is completely absent in patients with Type I diabetes.
[18] Consistently high blood glucose levels can lead to organ damage, neuropathy, blindness, cardiovascular issues and bone and joint problems.
One theory is that the alpha cells have become resistant to the inhibitory effects of glucose and insulin and do not respond properly to them.
On the other hand, a large number of reviewers[52] are uncertain whether these are separate effects, instead questioning the validity of Li on the basis of Ackermann and van der Meulen – perhaps GABA receptor agonists as a whole are not β-cell-ergic.
[53] Coppieters et al., 2020 goes further, highlighting Ackermann and van der Meulen as publications that catch an unreplicatable scientific result, Li.